id: Q15125
gene_symbol: EBP
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  EBP (3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase; sterol Delta8-Delta7 isomerase;
  EC 5.3.3.5), historically identified as the emopamil-binding protein, is a multi-pass
  integral membrane enzyme of the endoplasmic reticulum that catalyses a post-lanosterol
  step of cholesterol biosynthesis. It isomerises the Delta(8) double bond of sterol
  intermediates to the Delta(7) position, converting zymostenol to lathosterol (in the
  modified Kandutsch-Russell pathway) and zymosterol to cholesta-7,24-dien-3beta-ol (in the
  Bloch pathway). The protein localises predominantly to the endoplasmic reticulum membrane
  and the nuclear envelope, and it possesses four transmembrane helices and an EXPERA domain
  characteristic of the EBP family. Beyond its enzymatic role, EBP is a high-affinity binding
  protein for emopamil and related sigma-receptor/antiischemic ligands, and it is a component
  of the microsomal antiestrogen binding site (AEBS), a complex with DHCR7 that carries
  cholesterol-5,6-epoxide hydrolase (ChEH) activity and is a target of tamoxifen. Loss of
  isomerase activity causes X-linked dominant chondrodysplasia punctata 2 (CDPX2 /
  Conradi-Hunermann-Happle syndrome), characterised by accumulation of 8-dehydrocholesterol
  and 8(9)-cholestenol, chondrodysplasia punctata, ichthyosis, cataracts and short stature;
  hypomorphic hemizygous variants in males cause MEND syndrome.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10391218
  title: Mutations in a delta 8-delta 7 sterol isomerase in the tattered mouse and
    X-linked dominant chondrodysplasia punctata. jderry@immunex.com.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Identifies delta8-delta7 sterol isomerase (Ebp) mutations in the tattered mouse and
      in human X-linked dominant chondrodysplasia punctata (CDPX2); supports the isomerase
      function and disease link.
- id: PMID:10391219
  title: Mutations in the gene encoding 3 beta-hydroxysteroid-delta 8, delta 7-isomerase
    cause X-linked dominant Conradi-Hünermann syndrome.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Demonstrates EBP mutations in CDPX2 probands with accumulated 8(9)-cholestenol and
      8-dehydrocholesterol, functional validation in a sterol-delta8-isomerase-deficient
      yeast strain; directly establishes the isomerase function and disease.
- id: PMID:10406945
  title: Colocalization of sterol isomerase and sigma(1) receptor at endoplasmic reticulum
    and nuclear envelope level.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Subcellular localization of human sterol isomerase (EBP) to ER, nuclear envelope, and
      redistribution to cytoplasmic vesicles at mitosis; primary source for CC annotations.
- id: PMID:12760743
  title: Cloning of an emopamil-binding protein (EBP)-like protein that lacks sterol
    delta8-delta7 isomerase activity.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Although the paper's focus is the EBPL paralog, the full text characterizes EBP's own
      isomerase activity (EC 5.3.3.5) via mutagenesis of Y111, M121, F189; UniProt cites it
      as an EC 5.3.3.5 catalytic-activity source for EBP.
- id: PMID:20615952
  title: Identification and pharmacological characterization of cholesterol-5,6-epoxide
    hydrolase as a target for tamoxifen and AEBS ligands.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Establishes that the AEBS is a hetero-oligomeric complex of EBP (D8D7I) and DHCR7 that
      carries cholesterol-5,6-epoxide hydrolase activity; supports the ChEH annotation as a
      complex-level, non-core activity.
- id: PMID:25910212
  title: Widespread macromolecular interaction perturbations in human genetic disorders.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      High-throughput interactome perturbation study; source of a generic protein binding
      (GO:0005515) IPI. Uninformative as to EBP's molecular function.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Large-scale binary interactome map (HuRI); source of generic protein binding and
      identical protein binding IPIs. The self-interaction is consistent with the documented
      EBP homodimer.
- id: PMID:7706302
  title: Phenylalkylamine Ca2+ antagonist binding protein. Molecular cloning, tissue
    distribution, and heterologous expression.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Molecular cloning of EBP; predicts four transmembrane segments and a C-terminal
      ER-retrieval signal. Supports ER membrane localization (used as ISM source in GOA).
- id: PMID:8798407
  title: Emopamil-binding protein, a mammalian protein that binds a series of structurally
    diverse neuroprotective agents, exhibits delta8-delta7 sterol isomerase activity
    in yeast.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Demonstrates that EBP is the ER-resident delta8-delta7 sterol isomerase by functional
      complementation of a yeast isomerase deficiency; primary catalytic-activity source.
- id: PMID:9894009
  title: Histidine77, glutamic acid81, glutamic acid123, threonine126, asparagine194,
    and tryptophan197 of the human emopamil binding protein are required for in vivo
    sterol delta 8-delta 7 isomerization.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Ala-scanning mutagenesis identifying catalytic residues of human EBP; confirms sterol
      Delta8-Delta7 isomerase activity (EC 5.3.3.5).
- id: Reactome:R-HSA-195690
  title: Zymosterol is isomerized to cholesta-7,24-dien-3beta-ol
  findings: []
- id: Reactome:R-HSA-6807047
  title: Cholesterol biosynthesis via desmosterol (Bloch pathway)
  findings: []
- id: Reactome:R-HSA-6807052
  title: EBP isomerizes ZYMSTNL to LTHSOL
  findings: []
- id: Reactome:R-HSA-9969901
  title: Cholesterol biosynthesis from zymosterol (modified Kandutsch-Russell pathway)
  findings: []
- id: file:human/EBP/EBP-uniprot.txt
  title: UniProtKB Q15125 (EBP_HUMAN) record
  findings: []
existing_annotations:
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      EBP is an ER-resident membrane enzyme; the phylogenetic (IBA) ER localization is
      correct. ER membrane is the more precise, core location, so this broader ER term is
      kept as non-core.
    action: KEEP_AS_NON_CORE
    reason: >-
      ER localization is well supported experimentally, but the endoplasmic reticulum
      membrane (GO:0005789) captures the precise compartment for this multi-pass membrane
      enzyme; this broader term is retained but non-core.
    supported_by:
    - reference_id: PMID:8798407
      supporting_text: This endoplasmic reticulum-resident membrane protein
- term:
    id: GO:0006695
    label: cholesterol biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      EBP catalyses a post-lanosterol step of cholesterol biosynthesis; the IBA involvement
      in cholesterol biosynthetic process is a core biological-process annotation.
    action: ACCEPT
    reason: >-
      The sterol Delta8-Delta7 isomerization catalysed by EBP is an intermediate step in the
      conversion of lanosterol to cholesterol, well supported across orthologs and by human
      disease genetics.
    supported_by:
    - reference_id: PMID:10391219
      supporting_text: catalyses an intermediate step in the conversion of lanosterol to cholesterol
- term:
    id: GO:0000247
    label: C-8 sterol isomerase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      C-8 sterol isomerase activity is the core molecular function of EBP, moving the Delta(8)
      double bond to Delta(7). The phylogenetic annotation matches the biochemically
      demonstrated activity.
    action: ACCEPT
    reason: >-
      EBP is the sterol Delta8-Delta7 (C-8 sterol) isomerase; activity was demonstrated by
      yeast complementation and mutagenesis and is the enzyme's defining function.
    supported_by:
    - reference_id: PMID:8798407
      supporting_text: catalyzes the conversion of delta8-sterols to their corresponding
    - reference_id: PMID:9894009
      supporting_text: exhibits sterol Delta8-Delta7
- term:
    id: GO:0004769
    label: steroid Delta-isomerase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Steroid Delta-isomerase activity is the more general parent of the C-8 sterol isomerase
      activity that EBP performs; the IBA annotation is consistent with the demonstrated
      function.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a broader grouping term for the sterol double-bond isomerase activity; the
      specific C-8 sterol isomerase activity (GO:0000247) is the core molecular function, so
      the general term is retained as non-core.
    supported_by:
    - reference_id: PMID:9894009
      supporting_text: exhibits sterol Delta8-Delta7
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      EBP is detected on the nuclear envelope in addition to the ER, consistent with the
      SubCell-vocabulary IEA mapping.
    action: KEEP_AS_NON_CORE
    reason: >-
      Nuclear-envelope localization is experimentally documented (PMID:10406945) but is
      secondary to the ER membrane, where the enzyme principally acts.
    supported_by:
    - reference_id: PMID:10406945
      supporting_text: associated with the endoplasmic reticulum and with the
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      ER membrane is the core subcellular location of this multi-pass membrane enzyme; the
      SubCell IEA mapping is correct.
    action: ACCEPT
    reason: >-
      EBP is a multi-pass endoplasmic reticulum membrane protein where sterol isomerization
      occurs; supported experimentally and by the four predicted transmembrane helices.
    supported_by:
    - reference_id: PMID:8798407
      supporting_text: This endoplasmic reticulum-resident membrane protein
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: located_in
  review:
    summary: >-
      Generic membrane localization from the InterPro-to-GO mapping. EBP is indeed an
      integral membrane protein, but this parent term is uninformative given the specific ER
      membrane annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The unqualified membrane term is subsumed by the more precise endoplasmic reticulum
      membrane (GO:0005789) annotation and adds no information.
    supported_by:
    - reference_id: PMID:7706302
      supporting_text: Hydrophobicity plots predicted four transmembrane segments
- term:
    id: GO:0016125
    label: sterol metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      Sterol metabolic process is a correct but general parent of the cholesterol
      biosynthetic process in which EBP acts.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct high-level process term; the specific role is in cholesterol biosynthesis
      (GO:0006695), so this broader term is retained as non-core.
    supported_by:
    - reference_id: PMID:8798407
      supporting_text: Delta8-delta7 sterol isomerase is an essential enzyme on the sterol biosynthesis
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      EBP redistributes to cytoplasmic vesicles specifically during mitosis when the nuclear
      membranes break down; a transient, cell-cycle-dependent localization.
    action: KEEP_AS_NON_CORE
    reason: >-
      Experimentally observed only during mitosis (PMID:10406945); not the resting/core
      compartment for enzymatic function.
    supported_by:
    - reference_id: PMID:10406945
      supporting_text: delocalized during the cell cycle at the mitosis step when the nuclear membranes
- term:
    id: GO:0033963
    label: cholesterol-5,6-oxide hydrolase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      As a component of the AEBS complex with DHCR7, EBP contributes to cholesterol-5,6-epoxide
      hydrolase (ChEH) activity, a tamoxifen-inhibited activity distinct from its isomerase
      function.
    action: KEEP_AS_NON_CORE
    reason: >-
      ChEH activity is a genuine, experimentally supported activity of the EBP-DHCR7 (AEBS)
      complex, but is a secondary/complex-level function; the precise contribution of each
      subunit is not resolved. Retained as non-core rather than as the enzyme's core MF.
    supported_by:
    - reference_id: PMID:20615952
      supporting_text: cholesterol-5,6-epoxide hydrolase (ChEH)
- term:
    id: GO:0047750
    label: cholestenol delta-isomerase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Cholestenol delta-isomerase activity (EC 5.3.3.5, lathosterol <-> 5alpha-cholest-8-en-
      3beta-ol) is precisely the EBP-catalysed Delta8-Delta7 isomerase reaction.
    action: ACCEPT
    reason: >-
      This EC 5.3.3.5 term corresponds exactly to EBP's demonstrated sterol Delta8-Delta7
      isomerase activity; it is a valid alternative label for the core molecular function.
    supported_by:
    - reference_id: PMID:9894009
      supporting_text: isomerase activity (EC 5.3.3.5) upon heterologous expression in a sterol
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25910212
  qualifier: enables
  review:
    summary: >-
      Generic protein binding from a high-throughput interactome-perturbation screen; not
      informative about EBP's molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Bare protein binding (GO:0005515) from a large-scale interactome study conveys no
      specific functional information and is subsumed by the enzyme's characterized activity;
      marked as over-annotated rather than removed, per experimental-IPI policy.
    supported_by:
    - reference_id: PMID:25910212
      supporting_text: Widespread macromolecular interaction perturbations in human genetic disorders
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      Generic protein binding from the HuRI binary interactome map; uninformative as to
      molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Bare protein binding (GO:0005515) from a systematic interactome screen adds no
      functional specificity; marked as over-annotated rather than removed.
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: A reference map of the human binary protein interactome
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      EBP self-associates as a homodimer; identical protein binding is consistent with the
      documented EBP-EBP interaction and cross-linking-induced homodimerization.
    action: KEEP_AS_NON_CORE
    reason: >-
      Homodimerization is corroborated by the UniProt IntAct Q15125-Q15125 self-interaction
      and by chemical cross-linking data; a real but non-core property of the enzyme.
    supported_by:
    - reference_id: PMID:12760743
      supporting_text: Chemical cross-linking induced homodimerization of EBPL and EBP
- term:
    id: GO:0000247
    label: C-8 sterol isomerase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: >-
      Electronic ortholog transfer of the core C-8 sterol isomerase activity; consistent with
      the experimentally demonstrated function.
    action: ACCEPT
    reason: >-
      Duplicate of the core molecular function via Ensembl Compara ortholog transfer; correct.
    supported_by:
    - reference_id: PMID:8798407
      supporting_text: catalyzes the conversion of delta8-sterols to their corresponding
- term:
    id: GO:0006695
    label: cholesterol biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Electronic annotation to cholesterol biosynthetic process; matches the enzyme's role in
      post-lanosterol cholesterol synthesis.
    action: ACCEPT
    reason: >-
      Consistent with the experimentally and phylogenetically supported role of EBP in
      cholesterol biosynthesis.
    supported_by:
    - reference_id: PMID:10391219
      supporting_text: catalyses an intermediate step in the conversion of lanosterol to cholesterol
- term:
    id: GO:0006695
    label: cholesterol biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6807047
  qualifier: involved_in
  review:
    summary: >-
      Reactome traceable-author annotation placing EBP in the Bloch (via desmosterol)
      cholesterol biosynthesis pathway.
    action: ACCEPT
    reason: >-
      EBP isomerizes zymosterol to cholesta-7,24-dien-3beta-ol in the Bloch pathway; a core
      cholesterol-biosynthesis process annotation.
    supported_by:
    - reference_id: Reactome:R-HSA-6807047
      supporting_text: Cholesterol biosynthesis via desmosterol (Bloch pathway)
- term:
    id: GO:0006695
    label: cholesterol biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9969901
  qualifier: involved_in
  review:
    summary: >-
      Reactome traceable-author annotation placing EBP in the modified Kandutsch-Russell
      cholesterol biosynthesis pathway (zymostenol to lathosterol).
    action: ACCEPT
    reason: >-
      EBP isomerizes zymostenol to lathosterol in the modified Kandutsch-Russell pathway; a
      core cholesterol-biosynthesis process annotation.
    supported_by:
    - reference_id: Reactome:R-HSA-9969901
      supporting_text: Cholesterol biosynthesis from zymosterol (modified Kandutsch-Russell
- term:
    id: GO:0004769
    label: steroid Delta-isomerase activity
  evidence_type: EXP
  original_reference_id: PMID:10391218
  qualifier: enables
  review:
    summary: >-
      Experimental identification of EBP (Ebp) as the delta8-delta7 sterol isomerase mutated
      in the tattered mouse and CDPX2, supporting the (general) steroid Delta-isomerase
      activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      The essence (sterol double-bond isomerase) is correct, but the specific C-8 sterol
      isomerase activity (GO:0000247) captures the function more precisely; this broader term
      is retained as non-core.
    supported_by:
    - reference_id: PMID:10391218
      supporting_text: delta8-delta7 sterol isomerase
- term:
    id: GO:0004769
    label: steroid Delta-isomerase activity
  evidence_type: EXP
  original_reference_id: PMID:10391219
  qualifier: enables
  review:
    summary: >-
      Experimental support for EBP as 3beta-hydroxysteroid-delta8,delta7-isomerase from CDPX2
      genetics and yeast functional validation; the general steroid Delta-isomerase grouping
      is correct.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct grouping term; the specific C-8 sterol isomerase activity (GO:0000247) is the
      core molecular function, so this parent is retained as non-core.
    supported_by:
    - reference_id: PMID:10391219
      supporting_text: defects in sterol-delta8-isomerase cause CDPX2
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      Immunofluorescence-based ER localization of EBP; correct but broader than the ER
      membrane, where the enzyme resides.
    action: KEEP_AS_NON_CORE
    reason: >-
      Direct assay supports ER localization; ER membrane (GO:0005789) is the precise core
      compartment, so this broader term is retained as non-core.
    supported_by:
    - reference_id: PMID:10406945
      supporting_text: associated with the endoplasmic reticulum and with the
- term:
    id: GO:0031965
    label: nuclear membrane
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      Nuclear-membrane localization from immunofluorescence, consistent with EBP detection on
      the outer and inner nuclear-envelope membranes.
    action: KEEP_AS_NON_CORE
    reason: >-
      Experimentally documented but secondary to the ER membrane; retained as non-core.
    supported_by:
    - reference_id: PMID:10406945
      supporting_text: associated with the endoplasmic reticulum and with the
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: EXP
  original_reference_id: PMID:10406945
  qualifier: located_in
  review:
    summary: >-
      EBP redistributes to cytoplasmic vesicles during mitosis, a transient cell-cycle
      localization directly observed by microscopy.
    action: KEEP_AS_NON_CORE
    reason: >-
      Observed only during mitosis when nuclear membranes disperse; not the resting core
      compartment.
    supported_by:
    - reference_id: PMID:10406945
      supporting_text: delocalized during the cell cycle at the mitosis step when the nuclear membranes
- term:
    id: GO:0047750
    label: cholestenol delta-isomerase activity
  evidence_type: EXP
  original_reference_id: PMID:12760743
  qualifier: enables
  review:
    summary: >-
      Experimental characterization of EBP's EC 5.3.3.5 sterol delta8-delta7 isomerase
      (cholestenol delta-isomerase) activity via mutagenesis.
    action: ACCEPT
    reason: >-
      This EC 5.3.3.5 term is exactly EBP's demonstrated Delta8-Delta7 isomerase activity; a
      valid label for the core molecular function.
    supported_by:
    - reference_id: PMID:12760743
      supporting_text: 3beta-hydroxysteroid sterol delta8-delta7 isomerase activity
- term:
    id: GO:0047750
    label: cholestenol delta-isomerase activity
  evidence_type: EXP
  original_reference_id: PMID:8798407
  qualifier: enables
  review:
    summary: >-
      Functional yeast-complementation evidence that EBP catalyses the delta8-delta7 sterol
      isomerization (EC 5.3.3.5).
    action: ACCEPT
    reason: >-
      Directly demonstrates the core Delta8-Delta7 isomerase (cholestenol delta-isomerase,
      EC 5.3.3.5) activity of EBP.
    supported_by:
    - reference_id: PMID:8798407
      supporting_text: catalyzes the conversion of delta8-sterols to their corresponding
- term:
    id: GO:0047750
    label: cholestenol delta-isomerase activity
  evidence_type: EXP
  original_reference_id: PMID:9894009
  qualifier: enables
  review:
    summary: >-
      Ala-scanning mutagenesis confirming EBP's sterol Delta8-Delta7 isomerase (EC 5.3.3.5)
      activity and identifying its catalytic residues.
    action: ACCEPT
    reason: >-
      Direct experimental confirmation of the core EC 5.3.3.5 isomerase activity.
    supported_by:
    - reference_id: PMID:9894009
      supporting_text: isomerase activity (EC 5.3.3.5) upon heterologous expression in a sterol
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:10406945
  qualifier: is_active_in
  review:
    summary: >-
      Direct-assay evidence that EBP is active at the endoplasmic reticulum membrane, its
      core catalytic compartment.
    action: ACCEPT
    reason: >-
      ER membrane is the site of the sterol isomerization reaction; is_active_in is the
      appropriate qualifier for this multi-pass membrane enzyme.
    supported_by:
    - reference_id: PMID:10406945
      supporting_text: associated with the endoplasmic reticulum and with the
- term:
    id: GO:0033963
    label: cholesterol-5,6-oxide hydrolase activity
  evidence_type: IMP
  original_reference_id: PMID:20615952
  qualifier: enables
  review:
    summary: >-
      EBP contributes to cholesterol-5,6-epoxide hydrolase (ChEH) activity as part of the
      AEBS complex with DHCR7; a tamoxifen-inhibited activity distinct from its isomerase
      role.
    action: KEEP_AS_NON_CORE
    reason: >-
      ChEH activity is a genuine, experimentally supported activity of the EBP-DHCR7 (AEBS)
      complex, but the precise contribution of each subunit is undefined and it is not the
      enzyme's core molecular function; retained as non-core per experimental-annotation
      policy.
    supported_by:
    - reference_id: PMID:20615952
      supporting_text: composed of 3beta-hydroxysterol-Delta8-Delta7-isomerase (D8D7I) and
- term:
    id: GO:0004769
    label: steroid Delta-isomerase activity
  evidence_type: IDA
  original_reference_id: PMID:10391219
  qualifier: enables
  review:
    summary: >-
      Direct-assay support (yeast expression of patient alleles) for EBP's sterol
      delta8-isomerase activity, under the general steroid Delta-isomerase grouping.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but general; the specific C-8 sterol isomerase activity (GO:0000247) is the
      core function, so this parent is retained as non-core.
    supported_by:
    - reference_id: PMID:10391219
      supporting_text: defects in sterol-delta8-isomerase cause CDPX2
- term:
    id: GO:0004769
    label: steroid Delta-isomerase activity
  evidence_type: IMP
  original_reference_id: PMID:10391219
  qualifier: enables
  review:
    summary: >-
      Mutational (patient-allele) evidence for EBP's steroid Delta-isomerase activity from
      CDPX2 genetics and yeast functional validation.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct general grouping term; the specific C-8 sterol isomerase activity (GO:0000247)
      captures the function precisely, so this parent is retained as non-core.
    supported_by:
    - reference_id: PMID:10391219
      supporting_text: defects in sterol-delta8-isomerase cause CDPX2
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: ISM
  original_reference_id: PMID:7706302
  qualifier: located_in
  review:
    summary: >-
      Sequence-model inference of ER membrane localization from the four predicted
      transmembrane segments and the C-terminal ER-retrieval signal.
    action: ACCEPT
    reason: >-
      Consistent with the experimentally confirmed ER membrane localization; the cloning
      paper predicted four transmembrane segments and an ER-retrieval motif.
    supported_by:
    - reference_id: PMID:7706302
      supporting_text: Hydrophobicity plots predicted four transmembrane segments
- term:
    id: GO:0008203
    label: cholesterol metabolic process
  evidence_type: IMP
  original_reference_id: PMID:10391219
  qualifier: involved_in
  review:
    summary: >-
      EBP loss-of-function (CDPX2) perturbs cholesterol metabolism, supporting involvement in
      the cholesterol metabolic process (parent of biosynthesis).
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but broader than cholesterol biosynthetic process (GO:0006695), which is the
      precise role; retained as non-core.
    supported_by:
    - reference_id: PMID:10391219
      supporting_text: catalyses an intermediate step in the conversion of lanosterol to cholesterol
- term:
    id: GO:0043931
    label: ossification involved in bone maturation
  evidence_type: IMP
  original_reference_id: PMID:10391219
  qualifier: involved_in
  review:
    summary: >-
      The skeletal (chondrodysplasia punctata) phenotype of CDPX2 reflects disrupted sterol
      biosynthesis; the authors infer a role for sterols in bone development.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a downstream developmental consequence of the enzyme's metabolic defect, not a
      direct molecular role of EBP in the ossification machinery; retained as a non-core
      pleiotropic/developmental annotation.
    supported_by:
    - reference_id: PMID:10391219
      supporting_text: defects in sterol-delta8-isomerase cause CDPX2 and suggest a role for sterols in
- term:
    id: GO:0000247
    label: C-8 sterol isomerase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: >-
      Sequence-similarity transfer of the core C-8 sterol isomerase activity; consistent with
      the experimentally demonstrated function.
    action: ACCEPT
    reason: >-
      Duplicate of the core molecular function via curated ortholog similarity; correct.
    supported_by:
    - reference_id: PMID:8798407
      supporting_text: catalyzes the conversion of delta8-sterols to their corresponding
- term:
    id: GO:0004769
    label: steroid Delta-isomerase activity
  evidence_type: IDA
  original_reference_id: PMID:9894009
  qualifier: enables
  review:
    summary: >-
      Direct-assay support for EBP's sterol Delta8-Delta7 isomerase activity via yeast
      expression and mutagenesis, under the general steroid Delta-isomerase grouping.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but general; the specific C-8 sterol isomerase activity (GO:0000247) is the
      core function, so this parent is retained as non-core.
    supported_by:
    - reference_id: PMID:9894009
      supporting_text: exhibits sterol Delta8-Delta7
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: IDA
  original_reference_id: PMID:10406945
  qualifier: located_in
  review:
    summary: >-
      Direct microscopy localizing EBP to the nuclear envelope (outer and inner membranes) in
      addition to the ER.
    action: KEEP_AS_NON_CORE
    reason: >-
      Experimentally documented but secondary to the ER membrane; retained as non-core.
    supported_by:
    - reference_id: PMID:10406945
      supporting_text: associated with the endoplasmic reticulum and with the
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:10406945
  qualifier: located_in
  review:
    summary: >-
      Direct microscopy localizing EBP to the endoplasmic reticulum; correct but broader than
      the ER membrane where the enzyme acts.
    action: KEEP_AS_NON_CORE
    reason: >-
      Direct assay supports ER localization; ER membrane (GO:0005789) is the precise core
      compartment, so this broader term is retained as non-core.
    supported_by:
    - reference_id: PMID:10406945
      supporting_text: associated with the endoplasmic reticulum and with the
- term:
    id: GO:0006695
    label: cholesterol biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:9894009
  qualifier: involved_in
  review:
    summary: >-
      Direct-assay evidence tying EBP's isomerase activity to cholesterol biosynthesis (yeast
      Delta5,7-sterol production); a core process annotation.
    action: ACCEPT
    reason: >-
      EBP catalyses an obligatory post-lanosterol isomerization step of cholesterol
      biosynthesis; directly supported.
    supported_by:
    - reference_id: PMID:8798407
      supporting_text: Delta8-delta7 sterol isomerase is an essential enzyme on the sterol biosynthesis
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-195690
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable-author annotation locating the EBP-catalysed zymosterol
      isomerization at the ER membrane.
    action: ACCEPT
    reason: >-
      Consistent with the experimentally confirmed ER membrane localization and site of
      catalysis.
    supported_by:
    - reference_id: Reactome:R-HSA-195690
      supporting_text: Zymosterol is isomerized to cholesta-7,24-dien-3beta-ol
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6807052
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable-author annotation locating the EBP-catalysed zymostenol-to-lathosterol
      isomerization at the ER membrane.
    action: ACCEPT
    reason: >-
      Consistent with experimentally confirmed ER membrane localization and site of catalysis.
    supported_by:
    - reference_id: Reactome:R-HSA-6807052
      supporting_text: EBP isomerizes ZYMSTNL to LTHSOL
core_functions:
- description: >-
    C-8 sterol isomerase (sterol Delta8-Delta7 isomerase, EC 5.3.3.5) activity at the
    endoplasmic reticulum membrane, catalysing an obligatory post-lanosterol step of
    cholesterol biosynthesis (zymostenol to lathosterol; zymosterol to
    cholesta-7,24-dien-3beta-ol).
  molecular_function:
    id: GO:0000247
    label: C-8 sterol isomerase activity
  directly_involved_in:
  - id: GO:0006695
    label: cholesterol biosynthetic process
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: PMID:8798407
    supporting_text: catalyzes the conversion of delta8-sterols to their corresponding
  - reference_id: PMID:9894009
    supporting_text: isomerase activity (EC 5.3.3.5) upon heterologous expression in a sterol
proposed_new_terms: []
suggested_questions:
- question: >-
    Within the AEBS (EBP-DHCR7) complex, does EBP itself contribute the catalytic
    cholesterol-5,6-epoxide hydrolase activity, or is it a scaffolding/regulatory partner of
    DHCR7?
suggested_experiments:
- description: >-
    Reconstitute purified EBP and DHCR7 separately and together in defined liposomes and
    assay ChEH activity to resolve which subunit carries the epoxide-hydrolase catalysis.
- description: >-
    Use the available cryo-EM/X-ray structures (PDB 6OHT, 8W0R) to model catalytic-residue
    (H77, E81, E123, T126, N194, W197) positioning relative to bound sterol and validate by
    structure-guided mutagenesis of the Delta8-Delta7 isomerization.